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Biomedical subjects

J Hirate

Publications and source records attributed to J Hirate.

36 records · Page 2Linked to original sources
PubMed1984

Salivary excretion of urea in dogs.

The salivary excretion of urea was investigated by collecting parotid saliva (Pr) and mandibular-sublingual saliva (MS) separately in beagle dogs. (1) After intravenous administration of urea (1.5 g/kg), urea concentrations in both Pr and MS were well correlated to but were lower than those in plasma. Urea concentrations in MS were significantly lower than those in Pr (p less than 0.05), indicating that there was glandular difference in salivary excretion of urea. (2) This glandular difference was not explained by Matin's equation, even if all variation factors in this equation were considered. (3) At relatively low salivary flow rates, the increase in saliva/plasma urea concentration ratio (S/P ratio) for both Pr and MS was found in the experiments for endogenous urea. (4) At relatively low salivary flow rates, glandular difference was observed in the S/P ratios of sodium ion. (5) Salivary clearance of urea was highly dependent on salivary flow rate under stimulated condition for salivation, and mean value of the salivary clearance of urea was about 20% of its total body clearance.

Absorption↗
PubMed1984

Effect of hypothermia and ether anesthesia on the dispositions of creatinine and urea in mice.

Hypothermal mice were used under the anesthetized condition with ether to clarify the effect of diminished blood circulation on the dispositions of creatinine and urea which are considered to pass through the water-filled pores of biological membranes easily. The total body clearance of each chemical was considerably decreased in hypothermal mice compared with normal mice. This was considered to be caused by the decrease of glomerular filtration rate. The whole-body autoradiograms obtained following intravenous administration of 14C-urea and the rate of muscular blood flow showed that the transfer of urea from blood to muscle was apparently delayed by the decrease of muscular blood flow rate. However, the transfer of creatinine to muscle was not influenced by the change of muscular blood flow rate. This difference between creatinine and urea might be related to the higher permeability of muscular cell membrane to urea than to creatinine.

Anesthesia↗
PubMed1984

Disposition of salicylic acid in analbuminemic rats.

To clarify the role of albumin in the dispositions of drugs by in vivo experiment, analbuminemic rats were used and plasma-level analyses and whole-body autoradiography following intravenous administration of 14C-salicylic acid were carried out. The distribution volume of salicylic acid in analbuminemic rats (650 +/- 33 ml/kg) was remarkably larger than that in normal rats (180 +/- 3 ml/kg) (p less than 0.01). Whole-body autoradiograms demonstrated that transfer of salicylic acid from the blood to the liver, muscle and brain, especially to the liver, may be increased in analbuminemic rats. The increased distribution may be explained by the lack of plasma albumin, since the distribution of salicylic acid depends in part on plasma albumin binding. The total body clearance of salicylic acid in analbuminemic rats (12.2 +/- 1.4 ml/min/kg) was about 3.2 times that in normal rats (3.8 +/- 0.1 ml/min/kg) (p less than 0.01), suggesting that metabolic clearance and/or renal clearance is enhanced in analbuminemic rats. Increased extraction by the liver and/or the kidney due to increased free fraction in total (bound and unbound) plasma salicylic acid assumed to be responsible for this result.

Animals↗
PubMed1983

The change of disposition kinetics for creatinine and urea accompanied by growth in mice.

In order to clarify the change of disposition kinetics accompanied by growth, the whole-blood levels and whole-body autoradiography following intravenous administration of creatinine and urea, which are considered to pass through the water-filled pores of biological membranes easily, were investigated in 1-day-old, 1-week-old, 3-week-old and 8-week-old mice. For both creatinine and urea, the total body clearance was considerably lower in 1-day-old and 1-week-old mice than in more aged mice. Relatively lower renal clearance (i.e. rather incomplete renal function) in 1-day-old and 1-week-old mice was considered to be the major reason for this observation. Moreover, the lower metabolic clearance also seemed to be the cause in the case of urea, because the expiratory excretion of 14CO2 following the intravenous administration of 14C-urea was almost negligible in 1-day-old and 1-week-old mice in contrast to more aged (16-21%). The whole-body autoradiograms obtained following intravenous administration of 14C-creatinine indicated that creatinine was more rapidly transferred from blood to muscle in 1-day-old and 1-week-old mice, especially in 1-day-old mice, than in more aged mice. This might be caused by the difference in muscular blood flow rate or muscular cell membrane permeability to creatinine.

Aging↗
PubMed1983

The change of disposition kinetics for thiourea accompanied by growth in mice.

The whole blood levels and whole-body autoradiography following intravenous administration of thiourea, which is considered to covalently bind to the macromolecules in the body, were investigated in 1-day-old, 1-week-old, 3-week-old and 8-week-old mice in order to clarify the change of disposition kinetics accompanied by growth. The total body clearance for thiourea was remarkably lower in 1-day-old and 1-week-old mice than in more aged mice. The lower metabolic clearance as well as renal clearance in 1-day-old and 1-week-old mice seemed to be responsible for this observation. The whole-body autoradiograms obtained at 60 min following intravenous administration of 14C-thiourea showed the homogeneous distribution of radioactivity throughout the body in 1-day-old and 1-week-old mice and the high radioactivity localized in the liver and lung in more aged mice. This remarkable difference was assumed to be brought about by the difference in quantity of the macromolecules in the liver and lung which can covalently bind with thiourea. This assumption was supported by the result of gel filtration on Sephadex G-10 of the liver and lung homogenates.

Aging↗
PubMed1982

Absorption, distribution and elimination of creatinine and urea in hyperthyroid mice.

The absorption, distribution and elimination of creatinine and urea, which are considered to pass through the water-filled pores of biological membranes easily, were investigated in hyperthyroid mice to clarify the effects of enhanced blood circulation rate on drug behaviour in the body. The elimination rate constant in hyperthyroid mice was significantly and considerably larger than that in the control in both creatinine and urea (p less than 0.01). This result might be based on the increased urinary excretion rate of these two chemicals in hyperthyroid mice. The result of autoradiographic study indicated that creatinine was distributed more homogeneously in hyperthyroid mice than the control at 30 s and 2 min following intravenous administration. It was probably caused by the enhanced membrane permeability to creatinine due to some physiological changes (e.g. blood flow rate and pressure) or to a change of membrane itself. The gastrointestinal absorption of these two chemicals were also evaluated by the expiratory excretion of 14CO2 following oral administration. The results suggested that creatinine might be absorbed more slowly in hyperthyroid mice than in the control, and that in the case of urea such a difference in absorption might not exist.

Animals↗
PubMed1981

Distribution of creatinine following intravenous and oral administration to rats.

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

Administration, Oral↗
PubMed1981

Disposition of creatinine and urea in bilaterally nephrectomized rats.

Bilaterally nephrectomized rats were used to investigate the disposition of creatinine when renal function is acutely decreased. The percentage of radioactivity recovered in the expired air in 11 hours following intravenous administration of [carbonyl-14C] creatinine immediately and 24 hours after nephrectomy was 0.54 and 3.24% respectively, and these values were significantly different (p less than 0.05). As it was considered that expiratory excretion is one of the major elimination routes in nephrectomized rats, mechanism of expiratory excretion was investigated by incubating [carbonyl-14C] creatinine with the intestinal contents of the rats chronically loaded with creatinine [carbonyl-14C] Creatinine was completely metabolized in that intestinal contents, but 14CO2 was not produced. When the mixture of the metabolites was administered orally or intravenously to chronically creatinine loaded rats, however, about 50% of the total radioactivity was excreted into the expired air in 5 hours. Furthermore, biliary excretion of the radioactivity following intravenous administration of [carbonyl-14] creatinine in the nephrectomized rats was much greater than that in normal rats. These results indicate that expiratory excretion following intravenous administration [carbonyl-14C] creatinine to nephrectomized rats would arise following intestinal absorption of the creatinine metabolites, which seem to be produced by intestinal microflora after biliary excretion of creatinine. The change of disposition for urea by bilaterally nephrectomy was also studied to compare with that for creatinine.

Administration, Oral↗
PubMedDate not supplied

Further observations on the disposition characteristics of salicylic acid in analbuminemic rats.

The disposition characteristics of salicylic acid (SA) were investigated in analbuminemic rats after intravenous bolus injection of 10 and 173 mg kg-1 of SA to study the effects of plasma protein binding on drug disposition. Following the administration of 10 mg kg-1 of SA, total body SA clearance (CL) was markedly faster and its apparent volume of distribution (Vd) significantly greater in the analbuminemic rats in comparison to the controls. Further, the apparent elimination rate constant (kj) was two-fold greater and the corresponding elimination half-life (t 1/2) shorter in the rats with low plasma albumin. Whole body autoradiograms obtained following the administration of 14C-salicylic acid demonstrated that the tissue distribution of SA was greater in the analbuminemic rats which was in agreement with the larger Vd observed in this group of rats. After the administration of 173 mg kg-1 of SA, no differences in CL, Vd, kk or t 1/2 were noted between the analbuminemic and control rats. Dose-dependent SA disposition was observed in both the analbuminemic and control rats with the effects being more pronounced in the rats with low plasma albumin. The results suggested that the disposition characteristics of SA were markedly altered in the presence of low plasma albumin concentrations due to reduced plasma SA protein binding.

Animals↗
PubMedDate not supplied

Gastrointestinal, liver, and lung extraction ratio of acetaminophen in the rat after high dose administration.

The pharmacokinetics of acetaminophen was examined in rats after administration of a single dose of 200 mg kg-1 by the intra-arterial, intravenous, portal vein, and oral routes. Levels of acetaminophen and its two major metabolites, acetaminophen-glucuronide and acetaminophen-sulfate, were quantitated in plasma at various time points for about 5 h after drug administration. The relative contribution of the gastrointestinal tract, liver, and lung to the oral extraction ratio (first-pass effect after oral absorption) was determined. A mean oral extraction ratio of 0.49 was obtained. The mean relative extraction ratio of the gastrointestinal tract, liver, and lung were 0.52, 0.07, and 0, respectively, indicating a major contribution due to the gastrointestinal tract. This is in contrast to earlier studies which have indicated negligible contribution by the gastrointestinal tract to the oral first-pass effect when lower doses were utilized. These results suggest that the relative contribution of the gastrointestinal tract and liver to the oral first-pass effect of acetaminophen may be dose-dependent.

Acetaminophen↗